TY - JOUR AU - Bózsity-Faragó, Noémi AU - Nagy, Viktória AU - Szabó, Johanna AU - Pálházi, Balázs AU - Kele, Zoltán AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Zupkó, István AU - Minorics, Renáta AU - Mernyák, Erzsébet TI - Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 15 SN - 1661-6596 DO - 10.3390/ijms25084274 UR - https://m2.mtmt.hu/api/publication/34789041 ID - 34789041 AB - Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges. LA - English DB - MTMT ER - TY - JOUR AU - Gáborová, Mária AU - Vágvölgyi, Máté AU - Tayeb, Bizhar Ahmed AU - Minorics, Renáta AU - Zupkó, István AU - Jurček, Ondřej AU - Béni, Szabolcs AU - Kubínová, Renata AU - Balogh, György Tibor AU - Hunyadi, Attila TI - Diterpenes Isolated from Three Different Plectranthus Sensu Lato Species and Their Antiproliferative Activities against Gynecological and Glioblastoma Cancer Cells JF - ACS OMEGA J2 - ACS OMEGA PY - 2024 SN - 2470-1343 DO - 10.1021/acsomega.4c00800 UR - https://m2.mtmt.hu/api/publication/34779108 ID - 34779108 LA - English DB - MTMT ER - TY - JOUR AU - Ozsvár, Dániel AU - Bózsity-Faragó, Noémi AU - Zupkó, István AU - Szakonyi, Zsolt TI - Synthesis and Study of the Structure–Activity Relationship of Antiproliferative N-Substituted Isosteviol-Based 1,3-Aminoalcohols JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 17 PY - 2024 IS - 2 PG - 18 SN - 1424-8247 DO - 10.3390/ph17020262 UR - https://m2.mtmt.hu/api/publication/34666945 ID - 34666945 AB - Starting from isosteviol, a series of diterpenoid 1,3-aminoalcohol derivatives were prepared via stereoselective transformations. The acid-catalysed hydrolysis and rearrangement of natural stevioside produced isosteviol, which was transformed into the key intermediate methyl ester. In the next step, an 1,3-aminoalcohol library was prepared by the reductive amination of the intermediate 3-hydroxyaldehyde obtained from isosteviol in a two-step synthesis. To study the effect of the carboxylate ester function at position 4, the free carboxylic acid, benzyl ester and acryloyl ester analogues were prepared as elongated derivatives in comparison with our earlier results in this field. The antiproliferative activity of compounds against human tumour cell lines (A2780, HeLa, MCF-7 and MDA-MB-231) was investigated. In our preliminary study, the 1,3-aminoalcohol function with N-benzyl or (1H-imidazol-1-yl)-propyl substitution and benzyl ester moiety seemed essential for the reliable antiproliferative activity. The results obtained could be a good starting point to further functionalisation towards more efficient antiproliferative diterpenes. LA - English DB - MTMT ER - TY - JOUR AU - Khdar, Zein Alabdeen AU - Le Minh, Tam AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Szakonyi, Zsolt TI - Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohols regioisomers JF - RSC MEDICINAL CHEMISTRY J2 - RSC MED CHEM VL - 15 PY - 2024 IS - 3 SP - 874 EP - 887 PG - 14 SN - 2632-8682 DO - 10.1039/D3MD00665D UR - https://m2.mtmt.hu/api/publication/34577084 ID - 34577084 AB - A new library of allo -gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo -gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl... LA - English DB - MTMT ER - TY - JOUR AU - AHMED, Sara Hassan Hassan AU - Tayeb, Bizhar Ahmed AU - Gonda, Tímea AU - Girst, Gábor AU - Szőri, Kornél AU - Berkecz, Róbert AU - Zupkó, István AU - Minorics, Renáta AU - Hunyadi, Attila TI - Thymoquinone-protoflavone hybrid molecules as potential antitumor agents JF - PLOS ONE J2 - PLOS ONE VL - 19 PY - 2024 IS - 1 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0291567 UR - https://m2.mtmt.hu/api/publication/34541373 ID - 34541373 AB - We describe herein the synthesis of eight new ester-coupled hybrid compounds from thymoquinone and protoflavone building blocks, and their bioactivity testing against multiple cancer cell lines. Among the hybrids, compound 14 showed promising activities in all cell lines studied. The highest activities were recorded against breast cancer cell lines with higher selectivity to MDA-MB-231 as compared to MCF-7. Even though the hybrids were found to be completely hydrolysed in 24 h under cell culture conditions, compound 14 demonstrated a ca. three times stronger activity against U-87 glioblastoma cells than a 1:1 mixture of its fragments. Further, compound 14 showed good tumour selectivity: it acted 4.4-times stronger on U-87 cells than on MRC-5 fibroblasts. This selectivity was much lower, only ca. 1.3-times, when the cells were co-treated with a 1:1 mixture of its non-coupled fragments. Protoflavone-thymoquinone hybrids may therefore serve as potential new antitumor leads particularly against glioblastoma. LA - English DB - MTMT ER - TY - JOUR AU - Dembo, António AU - Ferenczi, Etelka AU - Jernei, Tamás AU - Bor, Andrea AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Varga, Szilárd AU - Csámpai, Antal TI - CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine–Chalcone Hybrids JF - MOLECULES J2 - MOLECULES VL - 29 PY - 2024 IS - 2 PG - 23 SN - 1420-3049 DO - 10.3390/molecules29020375 UR - https://m2.mtmt.hu/api/publication/34499406 ID - 34499406 AB - A series of novel triazole-tethered ferrocenoylamino-substituted cinchona–chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper–enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC50 values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart. LA - English DB - MTMT ER - TY - JOUR AU - Guillon, Jean AU - Le Borgne, Marc AU - Milano, Vittoria AU - Guédin-Beaurepaire, Aurore AU - Moreau, Stéphane AU - Pinaud, Noël AU - Ronga, Luisa AU - Savrimoutou, Solène AU - Albenque-Rubio, Sandra AU - Marchivie, Mathieu AU - Kalout, Haouraa AU - Walker, Charley AU - Chevallier, Louise AU - Buré, Corinne AU - Largy, Eric AU - Gabelica, Valérie AU - Mergny, Jean-Louis AU - Baylot, Virginie AU - Ferrer, Jacky AU - Idrissi, Yamina AU - Chevret, Edith AU - Cappellen, David AU - Desplat, Vanessa AU - Schelz, Zsuzsanna AU - Zupkó, István TI - New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 17 PY - 2024 IS - 1 SN - 1424-8247 DO - 10.3390/ph17010030 UR - https://m2.mtmt.hu/api/publication/34475300 ID - 34475300 AB - The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line. LA - English DB - MTMT ER - TY - JOUR AU - Girst, Gabor AU - Molnar, Barnabas AU - Frank, Eva AU - Minorics, Renáta AU - Zupko, Istvan AU - Wang, Hui-Chun AU - Hunyadi, Attila TI - Short Lecture "Preparation and antitumor investigation of new nature- inspired estradiol-protoflavone hybrids" JF - PLANTA MEDICA: NATURAL PRODUCTS AND MEDICINAL PLANT RESEARCH J2 - PLANTA MED VL - 89 PY - 2023 IS - 14 SP - 1278 EP - 1279 PG - 2 SN - 0032-0943 DO - 10.1055/s-0043-1773817 UR - https://m2.mtmt.hu/api/publication/34600758 ID - 34600758 LA - English DB - MTMT ER - TY - PAT AU - Csupor, Dezső AU - Zupkó, István AU - Hohmann, Judit AU - Kiss, Tivadar AU - Horváth, Attila TI - Gyomorfekély ellenes hatással rendelkező, hagyma leveléből kivont poliszacharidok, eljárás előállításukra és alkalmazásuk CY - Country:10001(1) PY - 2023 UR - https://m2.mtmt.hu/api/publication/34556245 ID - 34556245 LA - Hungarian DB - MTMT ER - TY - BOOK AU - Bakó, Pál AU - Domonkos, Norbert AU - Dovalovszkiné, Tóth Tünde AU - Andó, Bálint AU - Dobi, Ágnes AU - Ducza, Eszter AU - Elmer, Magdolna AU - Erdősi, Erika AU - Buzás, Norbert AU - Benkő, Sándor AU - Bitó, Tamás AU - Helembai, Kornélia AU - Joó, Gabriella AU - Kádár, Bettina Kata AU - Kapus, Katalin AU - Kiss, Éva AU - Kovách, Kornél AU - Lázár, Bence András AU - Budai, Éva AU - Márki, Árpád AU - Marton, Imelda AU - Miszlai, Péter AU - Mohos, András AU - Nagy-Grócz, Gábor AU - Németh, Anikó AU - Szakács, Júlia ED - Szatmári, Angelika AU - Tandori, Júlia AU - Tari, Gergely Róbert AU - Tobak, Orsolya ED - Vida, Anikó AU - Vincze, Anikó AU - Erdélyiné Oláh, Mónika AU - Festő, Blanka AU - Flach, István AU - Glózik, Ágnes AU - Godáné, Reisinger Karolina AU - Halmos, Helga AU - Horváth, Ádám AU - Kovácsné, Bilejov Brigitta AU - Meleg, Sándor Zsolt AU - Mező, Judit AU - Nagy, Erika AU - Oltványi, Beáta AU - Orosz, Annamária AU - Poszert, Anikó AU - Paulik, Edit AU - Tóth, Erika AU - Tóth, Renáta AU - Vajnai, Mária TI - Záróvizsga tesztgyűjtemény. Ápolás és betegellátás alapszak, ápoló szakirány TS - Ápolás és betegellátás alapszak, ápoló szakirány PB - Szegedi Tudományegyetem, Egészségtudományi és Szociális Képzési Kar CY - Szeged PY - 2023 SP - 715 SN - 9789633069707 UR - https://m2.mtmt.hu/api/publication/34496784 ID - 34496784 LA - Hungarian DB - MTMT ER -